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The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been treated with radium-226 applicators, and the mean absorbed dose to the breasts was 0.29 Gy (range <0.01-35.8 Gy). Two hundred forty-five breast cancers were diagnosed in the cohort during the period 1958-1993, and the standardized incidence ratio (SIR) was 1.20 (95% CI 1.06-1.36). Different dose-response models were tested, and a linear model gave the best fit. Neither age at exposure, breast dose rate, ovarian dose nor time since exposure had any statistically significant modifying effect, and breast dose was the only determinant of risk. The excess relative risk per gray (ERR/Gy) was 0.35 (95% CI 0.18-0.59), which is lower than in most other studies.

The risk of intracranial tumors after exposure to ionizing radiation during infancy has been studied in a pooled analysis of two Swedish hemangioma cohorts (n = 28,008). The mean absorbed intracranial dose was low (7 cGy, range 0-11.5 Gy). The cohorts were followed up in the Swedish Cancer Register for incident intracranial tumors during the period 1958-1993. Eighty-eight tumors were found in 86 individuals compared to 60.72 expected [standardized incidence ratio (SIR) 1.42, 95% confidence interval (CI) 1.13-1.75]. The SIR increased significantly in ascending dose categories (P = 0.02). Dose-response analyses were performed with Poisson regression methods. There was a significant effect of dose, and the dose-effect relationship was negatively modified by age at first treatment. This indicates a higher risk for those exposed earlier in life. A linear dose-response model modified by age at first treatment resulted in the best fit. The excess relative risk (ERR) was 2.7/Gy (95% CI 1.0-5.6). The ERR/Gy was 4.5 if the treatment was given before 5 months of age, 1.5 if it was given at 5-7 months and 0.4 if it was given later. The study thus strongly indicates that there exists a dose-response relationship between absorbed dose in the brain and the subsequent risk of developing an intracranial tumor and that the risk is higher among infants exposed at younger ages.

The possible impact of early gonadal irradiation on the results of future pregnancies is unclear. This study is based on the progeny of 17,393 women who were treated with irradiation for skin hemangiomas at the age of 18 months or less. The mean ovarian dose was 6 cGy, and the maximum was 8.55 Gy. Using Swedish central health registers, the outcome of delivery was studied in these women; 19,494 infants born were identified. The treated women deviated from the general population by having a longer education and by smoking less. This may explain a reduced risk for low birth weight and preterm birth (not related to radiation dose). Women with ovarian doses greater than 1 cGy had fewer infants than women with a lower ovarian dose. An excess of perinatal deaths was evident as well as a slight excess in the rate of malformation, but neither was related to dose. There was a statistically significant trend of an increasing rate of neural tube defects with ovarian dose, possibly a chance result of multiple statistical testing. Cleft lip/palate occurred at levels significantly below expectation. No increase in the rate of infants with Down syndrome or in childhood malignancies was detected. No major adverse results in outcome of delivery were seen after ovarian irradiation in childhood with the possible exception of neural tube defects.

From 1920 through 1959, 14,624 infants were exposed to ionizing radiation for skin hemangioma at Radiumhemmet. They were all less than 18 months old (mean 6 months) at the time of first exposure. The irradiated hemangiomas were located all over the body. The weighted bone marrow dose was on average 0.13 Gy (range < 0.01-4.6 Gy). During the period 1920-1986, 20 deaths from leukemia (11 childhood and 9 adult) were observed in the cohort compared with 17 expected during the same period. There were no significant associations between childhood leukemia and radiation dose. Despite the relatively large number of infants studied, the low average dose to bone marrow limited the possibility of detecting a small radiation risk as might be predicted from other radiation studies.

Between 1920 and 1959, 9675 women were irradiated in infancy for skin hemangioma at Radiumhemmet, Stockholm. They were exposed to low to moderate doses of ionizing radiation. The mean age at first exposure was 6 months and the mean absorbed dose to the breast anlage was 0.39 Gy (range <0.01-35.8 Gy). The breast cancer incidence was analyzed by record linkage with the Swedish Cancer Register for the period 1958-1986. Seventy-five breast cancers were found [standardized incidence ratio = 1.24; 95% confidence interval (CI) 0.98-1.54] after a mean absorbed dose of 1.5 Gy in the breasts with cancer. The analyses showed a significant dose-response relationship with a linear model estimate for the excess relative risk (ERR) of 0.38 at 1 Gy 95% CI 0.09-0.85). This relationship was not modified significantly by age at exposure or by dose to the ovaries. The ERR increased significantly with time after exposure and for > or = 50 years after exposure the ERR at 1 Gy was 2.25 (95% CI 0.59-5.62). The fitted excess absolute risk (EAR) was 22.9 per 10(4) breast-year gray. The breast absorbed dose and time after exposure were important risk determinants for breast cancer excess risk. Forty to 50 years of follow-up was necessary for the excess risk to be expressed. The study confirms previous findings that the breast anlage of female infants is sensitive to ionizing radiation.

Cancer incidence was studied in 14,351 subjects exposed to ionizing radiation for skin hemangioma at the Radiumhemmet, 1920-1959. Record-linkage was done with the Swedish Cancer Registry for the period 1958-1986. After a mean follow-up of 39 years, 300 cancers were observed and the standardized incidence ratio (SIR) was 1.11 (95% confidence interval (CI) 0.99-1.24). The absorbed dose to different organs varied from < 0.01 Gy to > 40 Gy. The thyroid cancer incidence was significantly increased (SIR = 2.28; 95% CI 1.33-3.65) and for cancer of the breast SIR was 1.24 (95% CI 0.98-1.54). Regarding pancreatic cancer and tumors of the endocrine glands the statistically significantly increased SIRs were based on a small number of cases and might therefore only be a coincidence. No confirmed increased incidence could be established for other cancer sites.

A Swedish cohort of 14,351 infants exposed to ionizing radiation for skin hemangioma was analyzed with respect to thyroid cancer risk. The subjects were irradiated during the period 1920-1959 and radiotherapy was given with beta particles, gamma rays and/or X rays. The mean absorbed dose to the thyroid was 0.26 Gy (range < 0.01-28.5 Gy). The cohort was matched with the Swedish Cancer Register for the period 1958-1986. Seventeen thyroid cancers were registered (standardized incidence ratio = 2.28; 95% confidence interval 1.33-3.65), and the mean thyroid absorbed dose in those subjects was 1.07 Gy (range < 0.01-4.34 Gy). The effect of different variables on the incidence of thyroid cancer was evaluated with Poisson regression. The excess in thyroid cancer began 19 years after radiotherapy and persisted at least 40 years after irradiation. A statistically significant dose-response relationship was found. The excess relative risk per gray was 4.92 (95% CI 1.26-10.2) and the excess absolute risk was 0.90 x 10(-4) per person-year gray. No significant difference in excess relative or absolute risk could be seen between the sexes.

Between 1920 and 1959, a total of 14,647 children younger than 18 months were treated at Radiumhemmet with ionizing radiation for skin hemangioma. Seventy-two percent of the children were treated with radium needles or tubes, which were put into glass capsules and then applied to the hemangioma. The absorbed doses to different organs have been measured in a tissue equivalent phantom, representing a 6-month-old child. For a standard treatment of 8 Gy to the hemangioma the mean absorbed doses to the brain, eye lens, parotid gland, thyroid, breast anlage and gonads from 28 different treatment areas were 0.03-0.2 Gy. The mean absorbed dose to the organs in younger (less than 2 months) and older (14-18 months) children were up to 50% higher (0.04-0.1 Gy) and 33% lower (0.02-0.06 Gy) respectively, than for a 6-month-old child. The uncertainty in organ absorbed doses for each patient depended mostly on the estimation of the distance between the applicator and the site.

A case-control study was conducted to investigate the possible association between absorbed dose and cancer risk in a cohort of 14,647 individuals (33% males and 67% females) less than 18 months old and irradiated for skin hemangioma between 1920 and 1959. The cases consisted of 56 breast cancers (in 55 patients), 14 thyroid cancers, 16 brain tumors and 8 tumors of bone and soft tissues. Four controls were matched to each case. They were matched for sex, age at treatment, treatment modality and treatment year. Absorbed doses were categorized in three exposure groups, less than 0.1 Gy, 0.1-0.4 Gy, and greater than or equal to 0.5 Gy, and odds ratios (OR) were estimated with the lowest exposure group as reference. A statistically significant positive dose-response relationship was found for thyroid cancer (OR: 1.0; 4.8; 4.3) and for tumors of bone and soft tissues (OR: 1.0; 1.6; 19.5). For breast cancer and brain tumors no significant dose-response relationship could be found. The median absorbed dose in the tumor sites among the cases of thyroid cancer, tumors of bone and soft tissues, breast cancer and brain tumors was 0.2 Gy, 0.3 Gy, 0.03 Gy and 0.04 Gy respectively. The dose was probably too low to detect any dose-response relationship for breast cancer and brain tumors.

The cancer incidence was studied in 18,030 patients (33% males, 67% females) with skin hemangioma who were admitted to Radiumhemmet, Karolinska Hospital, Stockholm, Sweden, 1920-1959. Radium-226 sources were used in 12,821 patients, x-ray therapy was used in 2,515 patients, and no radiotherapy was given to 2,694 patients. Cancer incidence in the cohort was searched by record linkage with the Swedish Cancer Register for the period 1958-1982. The median age was 6 months for the treated patients and 8 months for the patients not receiving radiotherapy. In the group treated with radium-226 or orthovoltage x rays (greater than or equal to 100-kV peak), 224 cancers were observed [relative risk (RR) = 1.18; 95% confidence interval (CI) = 1.03-1.35]. In patients given contact x rays, 10 cancers were observed (RR = 0.71; 95% CI = 0.34-1.30). In patients not treated with ionizing radiation, 34 cancers were observed (RR = 0.93; 95% CI = 0.64-1.29). In patients treated with radium-226 or orthovoltage x rays, an RR of 1.65 was observed for breast cancer (95% CI = 1.26-2.13) and an RR of 2.73 was found for soft tissue tumors (95% CI = 1.18-5.38). Patients with brain tumors, thyroid cancers, and bone tumors had received radiotherapy close to the tumor site more often than expected. For patients with breast cancer, no such difference was found. For cancers of the breast and thyroid, the RR was higher in patients given more than one treatment.

Radium and roentgen therapies for hemangiomas of the skin (mainly strawberry hemangiomas) were used between 1909 and 1959 at Radiumhemmet, Stockholm. The total number of admitted patients with hemangioma of the skin during this period was 20,012. About 90 per cent were treated with irradiation and radium therapy was the most commonly used modality. Needles, tubes and flat applicators containing radium were used. Roentgen therapy was given by using standard machines available at the time. A small number of patients were treated with 32P plaques. Most hemangiomas were located in the head-neck region (47%) and 30 per cent were located on the thorax and upper part of the abdomen. The median age at the first treatment was 6 months and 99 per cent of all patients were younger than 2 years of age at the time of treatment. The purpose of the investigation was to define a cohort, useful for studies on possible late effects following exposure to ionizing radiation in childhood.

Mortality was studied in 18,357 patients (33% males and 67% females) with skin hemangioma admitted to Radiumhemmet between 1920 and 1959. The treatments of the hemangiomas were performed by radium-226 sources (13,094 patients) or x-ray therapy (2,540 patients). In 2,723 patients no radiotherapy was given. The median age was 6 months for the treated patients and 8 months for the patients not receiving radiotherapy. Between 1920 and 1951 a total of 154 patients were reported dead. The cohort was matched with the Swedish Cause of Death Register between 1952 and 1985. During that period 504 died, in 146 patients the cause of death was cancer or leukemia. The total number of person-years at risk was 587,426. In patients treated with radium-226 or orthovoltage x-rays, 410 deaths occurred (standardized mortality ratio (SMR) = 1.07; ns). In patients given contact therapy 34 deaths occurred (SMR = 0.82; ns) and in the not irradiated group 60 deaths occurred (SMR = 0.78; ns). Patients treated with radium-226 or orthovoltage x-rays had an SMR of 1.34 for all cancers combined (p less than 0.05). For patients treated between 1920 and 1939 the SMR for cancer was 1.53 (p less than 0.05) as compared to an SMR of 1.16 (ns) for those treated between 1940 and 1959.